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Donor genetic determinant of thymopoiesis rs2204985 impacts clinical outcome after single HLA mismatched hematopoietic stem cell transplantation

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Donor genetic determinant of thymopoiesis rs2204985 impacts clinical outcome after single HLA mismatched hematopoietic stem cell transplantation. / Tsamadou, Chrysanthi; Gowdavally, Sowmya; Platzbecker, Uwe; Sala, Elisa; Valerius, Thomas; Wagner-Drouet, Eva; Wulf, Gerald; Kröger, Nicolaus; Murawski, Niels; Einsele, Hermann; Schaefer-Eckart, Kerstin; Freitag, Sebastian; Casper, Jochen; Kaufmann, Martin; Dürholt, Mareike; Hertenstein, Bernd; Klein, Stefan; Ringhoffer, Mark; Frank, Sandra; Neuchel, Christine; Rode, Immanuel; Schrezenmeier, Hubert; Mytilineos, Joannis; Fuerst, Daniel.

in: BONE MARROW TRANSPL, Jahrgang 57, Nr. 10, 10.2022, S. 1539-1547.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Tsamadou, C, Gowdavally, S, Platzbecker, U, Sala, E, Valerius, T, Wagner-Drouet, E, Wulf, G, Kröger, N, Murawski, N, Einsele, H, Schaefer-Eckart, K, Freitag, S, Casper, J, Kaufmann, M, Dürholt, M, Hertenstein, B, Klein, S, Ringhoffer, M, Frank, S, Neuchel, C, Rode, I, Schrezenmeier, H, Mytilineos, J & Fuerst, D 2022, 'Donor genetic determinant of thymopoiesis rs2204985 impacts clinical outcome after single HLA mismatched hematopoietic stem cell transplantation', BONE MARROW TRANSPL, Jg. 57, Nr. 10, S. 1539-1547. https://doi.org/10.1038/s41409-022-01751-1

APA

Tsamadou, C., Gowdavally, S., Platzbecker, U., Sala, E., Valerius, T., Wagner-Drouet, E., Wulf, G., Kröger, N., Murawski, N., Einsele, H., Schaefer-Eckart, K., Freitag, S., Casper, J., Kaufmann, M., Dürholt, M., Hertenstein, B., Klein, S., Ringhoffer, M., Frank, S., ... Fuerst, D. (2022). Donor genetic determinant of thymopoiesis rs2204985 impacts clinical outcome after single HLA mismatched hematopoietic stem cell transplantation. BONE MARROW TRANSPL, 57(10), 1539-1547. https://doi.org/10.1038/s41409-022-01751-1

Vancouver

Tsamadou C, Gowdavally S, Platzbecker U, Sala E, Valerius T, Wagner-Drouet E et al. Donor genetic determinant of thymopoiesis rs2204985 impacts clinical outcome after single HLA mismatched hematopoietic stem cell transplantation. BONE MARROW TRANSPL. 2022 Okt;57(10):1539-1547. https://doi.org/10.1038/s41409-022-01751-1

Bibtex

@article{87d8e8ac46f348b38bd9d5b14484667e,
title = "Donor genetic determinant of thymopoiesis rs2204985 impacts clinical outcome after single HLA mismatched hematopoietic stem cell transplantation",
abstract = "A common genetic variant within the T cell receptor alpha (TCRA)-T cell receptor delta (TCRD) locus (rs2204985) has been recently found to associate with thymic function. Aim of this study was to investigate the potential impact of donor rs2204985 genotype on patient's outcome after unrelated hematopoietic stem cell transplantation (uHSCT). 2016 adult patients were retrospectively analyzed. rs2204985 genotyping was performed by next generation sequencing, p < 0.05 was considered significant and donor rs2204985 GG/AG genotypes were set as reference vs. the AA genotype. Multivariate analysis of the combined cohort regarding the impact of donor's rs2204985 genotype indicated different risk estimates in 10/10 and 9/10 HLA matched transplantations. A subanalysis on account of HLA incompatibility revealed that donor AA genotype in single HLA mismatched cases (n = 624) associated with significantly inferior overall- (HR: 1.48, p = 0.003) and disease-free survival (HR: 1.50, p = 0.001). This effect was driven by a combined higher risk of relapse incidence (HR: 1.40, p = 0.026) and non-relapse mortality (HR: 1.38, p = 0.042). This is the first study to explore the role of rs2204985 in a clinical uHSCT setting. Our data suggest that donor rs2204985 AA genotype in combination with single HLA mismatches may adversely impact post-HSCT outcome and should thus be avoided.",
keywords = "Adult, Graft vs Host Disease/etiology, HLA Antigens/genetics, Hematopoietic Stem Cell Transplantation/adverse effects, Humans, Neoplasm Recurrence, Local, Receptors, Antigen, T-Cell, alpha-beta, Receptors, Antigen, T-Cell, gamma-delta, Retrospective Studies, Thrombopoiesis, Tissue Donors, Unrelated Donors",
author = "Chrysanthi Tsamadou and Sowmya Gowdavally and Uwe Platzbecker and Elisa Sala and Thomas Valerius and Eva Wagner-Drouet and Gerald Wulf and Nicolaus Kr{\"o}ger and Niels Murawski and Hermann Einsele and Kerstin Schaefer-Eckart and Sebastian Freitag and Jochen Casper and Martin Kaufmann and Mareike D{\"u}rholt and Bernd Hertenstein and Stefan Klein and Mark Ringhoffer and Sandra Frank and Christine Neuchel and Immanuel Rode and Hubert Schrezenmeier and Joannis Mytilineos and Daniel Fuerst",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
month = oct,
doi = "10.1038/s41409-022-01751-1",
language = "English",
volume = "57",
pages = "1539--1547",
journal = "BONE MARROW TRANSPL",
issn = "0268-3369",
publisher = "NATURE PUBLISHING GROUP",
number = "10",

}

RIS

TY - JOUR

T1 - Donor genetic determinant of thymopoiesis rs2204985 impacts clinical outcome after single HLA mismatched hematopoietic stem cell transplantation

AU - Tsamadou, Chrysanthi

AU - Gowdavally, Sowmya

AU - Platzbecker, Uwe

AU - Sala, Elisa

AU - Valerius, Thomas

AU - Wagner-Drouet, Eva

AU - Wulf, Gerald

AU - Kröger, Nicolaus

AU - Murawski, Niels

AU - Einsele, Hermann

AU - Schaefer-Eckart, Kerstin

AU - Freitag, Sebastian

AU - Casper, Jochen

AU - Kaufmann, Martin

AU - Dürholt, Mareike

AU - Hertenstein, Bernd

AU - Klein, Stefan

AU - Ringhoffer, Mark

AU - Frank, Sandra

AU - Neuchel, Christine

AU - Rode, Immanuel

AU - Schrezenmeier, Hubert

AU - Mytilineos, Joannis

AU - Fuerst, Daniel

N1 - © 2022. The Author(s).

PY - 2022/10

Y1 - 2022/10

N2 - A common genetic variant within the T cell receptor alpha (TCRA)-T cell receptor delta (TCRD) locus (rs2204985) has been recently found to associate with thymic function. Aim of this study was to investigate the potential impact of donor rs2204985 genotype on patient's outcome after unrelated hematopoietic stem cell transplantation (uHSCT). 2016 adult patients were retrospectively analyzed. rs2204985 genotyping was performed by next generation sequencing, p < 0.05 was considered significant and donor rs2204985 GG/AG genotypes were set as reference vs. the AA genotype. Multivariate analysis of the combined cohort regarding the impact of donor's rs2204985 genotype indicated different risk estimates in 10/10 and 9/10 HLA matched transplantations. A subanalysis on account of HLA incompatibility revealed that donor AA genotype in single HLA mismatched cases (n = 624) associated with significantly inferior overall- (HR: 1.48, p = 0.003) and disease-free survival (HR: 1.50, p = 0.001). This effect was driven by a combined higher risk of relapse incidence (HR: 1.40, p = 0.026) and non-relapse mortality (HR: 1.38, p = 0.042). This is the first study to explore the role of rs2204985 in a clinical uHSCT setting. Our data suggest that donor rs2204985 AA genotype in combination with single HLA mismatches may adversely impact post-HSCT outcome and should thus be avoided.

AB - A common genetic variant within the T cell receptor alpha (TCRA)-T cell receptor delta (TCRD) locus (rs2204985) has been recently found to associate with thymic function. Aim of this study was to investigate the potential impact of donor rs2204985 genotype on patient's outcome after unrelated hematopoietic stem cell transplantation (uHSCT). 2016 adult patients were retrospectively analyzed. rs2204985 genotyping was performed by next generation sequencing, p < 0.05 was considered significant and donor rs2204985 GG/AG genotypes were set as reference vs. the AA genotype. Multivariate analysis of the combined cohort regarding the impact of donor's rs2204985 genotype indicated different risk estimates in 10/10 and 9/10 HLA matched transplantations. A subanalysis on account of HLA incompatibility revealed that donor AA genotype in single HLA mismatched cases (n = 624) associated with significantly inferior overall- (HR: 1.48, p = 0.003) and disease-free survival (HR: 1.50, p = 0.001). This effect was driven by a combined higher risk of relapse incidence (HR: 1.40, p = 0.026) and non-relapse mortality (HR: 1.38, p = 0.042). This is the first study to explore the role of rs2204985 in a clinical uHSCT setting. Our data suggest that donor rs2204985 AA genotype in combination with single HLA mismatches may adversely impact post-HSCT outcome and should thus be avoided.

KW - Adult

KW - Graft vs Host Disease/etiology

KW - HLA Antigens/genetics

KW - Hematopoietic Stem Cell Transplantation/adverse effects

KW - Humans

KW - Neoplasm Recurrence, Local

KW - Receptors, Antigen, T-Cell, alpha-beta

KW - Receptors, Antigen, T-Cell, gamma-delta

KW - Retrospective Studies

KW - Thrombopoiesis

KW - Tissue Donors

KW - Unrelated Donors

U2 - 10.1038/s41409-022-01751-1

DO - 10.1038/s41409-022-01751-1

M3 - SCORING: Journal article

C2 - 35804057

VL - 57

SP - 1539

EP - 1547

JO - BONE MARROW TRANSPL

JF - BONE MARROW TRANSPL

SN - 0268-3369

IS - 10

ER -